The cytokine IL-4 is well studied for its role in driving allergic/asthmatic CD4 T cell responses: However its impact on CD8 T cells is much less clear. Building on published and preliminary data, we propose that IL-4 plays a critical and unexpected role in supporting the CD8 T cell response to pathogens. These findings will be investigated further to define the exact role of IL-4 responsiveness in the CD8 T cell response, and additional work will test the novel concept that IL-4 cytokine therapy could be used to enhance CD8 T cell protective immunity against malarial parasites. PUBLIC HEALTH RELEVANCE: Many infections are controlled by killer T lymphocytes (CTL), and there is a pressing need to improve vaccines that produce these cells. Here we look at an unexpected and interesting role for a serum protein called IL-4 which, based on our preliminary data, is critical to achieve a strong CTL response against infection. We test the role of IL-4 in the CTL responses against two pathogens (Listeria bacteria and malaria parasites) to establish what IL-4 does in controlling CTL responses (Aim 1) and test how this protein can be used to enhance CTL activity in order to prevent malarial disease.